Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-27278-4
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Funding
- NIH [R56AI116772, P20GM121176]
- American Lung Association [RG-268131]
- UNM Shared Flow Cytometry and High Throughput Screening Resource Center [NIH P30CA118100]
- American Association of Immunologists
- Ruby Fellowship
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Allergic asthma and obesity are major public health problems in the world. Recent Meta-analysis studies implicated a positive relationship between serum leptin, which is elevated in obese individuals, and the risk of asthma. However, it is not well understood how obesity-associated elevation of leptin increases the risk of asthma. In the current study, we have found that leptin induces the unfolded protein response factor XBP1s in an mTOR- and MAPK-dependent manner in pro-allergic TH2 cells; in vivo, mice fed with high fat diet had increased serum leptin as observed in human obese population and exacerbated asthmatic symptoms, associated with increased XBP1s expression in splenic CD4(+) T cells. XBP1s is required for leptin-mediated pro-allergic TH2 cell survival and cytokine production. Our results reveal a previously unappreciated insight that obesity-associated hyperleptinemia contributes to enhanced pro-allergic lymphocyte responses through induction of XBP1s, leading to exacerbation of allergic asthma.
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